Sonic hedgehog delivery from self-assembled nanofiber hydrogels reduces the fibrotic response in models of erectile dysfunction

自组装纳米纤维水凝胶中的音猬因子传递可降低勃起功能障碍模型中的纤维化反应

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作者:Shawn Choe, Dorina Veliceasa, Christopher W Bond, Daniel A Harrington, Samuel I Stupp, Kevin T McVary, Carol A Podlasek

Significance

We use self-assembling peptide amphiphiles (PA) as biological delivery vehicles to prevent cavernous nerve (CN) injury induced erectile dysfunction (ED). These versatile hydrogels were molecularly pre-programmed for sonic hedgehog (SHH) protein delivery, either from an injectable solution with fast, in situ assembly into a soft hydrogel, or by highly aligned monodomain nanofiber bundles. We used PAs to examine a novel neuronal component to collagen regulation and the role of SHH in the fibrotic response to CN injury. SHH perturbation in the penis or the CN, selectively impacts collagen, with SHH inhibition increasing and SHH treatment suppressing collagen. These results suggest that SHH treatment by PA has translational potential to suppress collagen induction and remodelling, an irreversible component of ED development.

Statement of significance

We use self-assembling peptide amphiphiles (PA) as biological delivery vehicles to prevent cavernous nerve (CN) injury induced erectile dysfunction (ED). These versatile hydrogels were molecularly pre-programmed for sonic hedgehog (SHH) protein delivery, either from an injectable solution with fast, in situ assembly into a soft hydrogel, or by highly aligned monodomain nanofiber bundles. We used PAs to examine a novel neuronal component to collagen regulation and the role of SHH in the fibrotic response to CN injury. SHH perturbation in the penis or the CN, selectively impacts collagen, with SHH inhibition increasing and SHH treatment suppressing collagen. These results suggest that SHH treatment by PA has translational potential to suppress collagen induction and remodelling, an irreversible component of ED development.

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